Joyce A. Cramer

Compare adverse events (AEs) in patients with epilepsy taking different antiepileptic drugs (AEDs) using standardized physician-completed questionnaires. Multicenter, observational, cross-sectional study in epilepsy patients aged ≥4 , stable on 1-2 AED(s) for ≥3 months. One thousand and nineteen patients were evaluated: 28.7% took newer, 71.3% older (or older + newer) AED(s); 56.9% monotherapy; 43.1% polytherapy. Overall, 68.3% reported ≥1 AE (61.3% newer; 71.1% older AEDs), most commonly: cognitive function disturbances, sedation, psychological problems. Patients taking newer AEDs were significantly less likely to report ≥1 AE (OR [95% CI]: 0.64 [0.46-0.89], P = 0.008). Treatment/dose changed at study visit: 22.8% (17.5% newer; 24.9% older AEDs) because of (newer/older); lack of efficacy (6.2%/7.8%); AEs (4.1/8.4%); absence of seizures (3.8/4.0%). Patients receiving levetiracetam or lamotrigine were significantly less likely to report AEs/modify treatment. Patients taking newer AEDs were significantly less likely to report AEs, although the non-randomized study design does not allow the lower rate of AEs to be attributed with certainty to the use of newer AEDs. A standardized AE questionnaire appeared useful for monitoring AEs/optimizing AED therapy.

All medications have some adverse effects, ranging from mild to acute and serious or chronic. Antiepileptic drugs (AEDs) differ in the type and severity of adverse effects, mostly during initiation and early treatment. Some concerns are related to pharmacodynamic tolerance often affected by the dose and rate of initiation, while other concerns are idiosyncratic responses to the drug (rare and not predictable). Thus, lack of tolerability is a common reason for changing medication, quantified in studies as treatment retention. Although adverse effects can occur with all AEDs, and CNS effects are most prevalent, selected effects are hallmarks of specific drugs. The failure of an AED regimen may be the result of unacceptable adverse effects (intolerance), inadequate seizure control (inefficacy) or a combination of both. Although some diminution in adverse effects is typical when a drug is used in monotherapy, the potential for most issues remains if they are dose-related or idiosyncratic. This article describes three categories of prevalent adverse effects (CNS, behavioral and general medical issues) comparing profiles of second- and third-generation AEDs.

The U.S. Food and Drug Administration (FDA) recently linked antiepileptic drug (AED) exposure to suicide-related behaviors based on meta-analysis of randomized clinical trials. We examined the relationship between suicide-related behaviors and different AEDs in older veterans receiving new AED monotherapy from the Veterans Health Administration (VA), controlling for potential confounders.

Objectives: To review studies of patient compliance/persistence with cardiovascular or antidiabetic medication published since the year 2000; to compare the methods used to measure compliance/persistence across studies; to compare reported compliance/persistence rates across therapeutic classes and to assess whether compliance/persistence correlates with clinical outcomes. Methods: English language papers published between January 2000 and November 2005 investigating patient compliance/persistence with cardiovascular or antidiabetic medication were identified through searches of the MEDLINE and EMBASE databases. Definitions and measurements of compliance/persistence were compared across therapeutic areas using contingency tables. Results: Of the 139 studies analysed, 32% focused on hypertension, 27% on diabetes and 13% on dyslipidaemia. The remainder covered coronary heart disease and cardiovascular disease (CVD) in general. The most frequently reported measure of compliance was the 12‐month medication possession ratio (MPR). The overall mean MPR was 72%, and the MPR did not differ significantly between treatment classes (range: 67–76%). The average proportion of patients with an MPR of > 80% was 59% overall, 64% for antihypertensives, 58% for oral antidiabetics, 51% for lipid‐lowering agents and 69% in studies of multiple treatments, again with no significant difference between treatment classes. The average 12‐month persistence rate was 63% and was similar across therapeutic classes. Good compliance had a positive effect on outcome in 73% of the studies examining clinical outcomes. Conclusions: Non‐compliance with cardiovascular and antidiabetic medication is a significant problem, with around 30% of days ‘on therapy’ not covered by medication and only 59% of patients taking medication for more than 80% of their days ‘on therapy’ in a year. Good compliance has a positive effect on clinical outcome, suggesting that the management of CVD may be improved by improving patient compliance.

To demonstrate that retrospective analyses of medication persistence require careful methodological approaches to assure accuracy and consistency across various types of databases. Bisphosphonates (BPs) are used as an example because of the availability of diverse dosing options that can create a unique set of challenges for persistence analyses. Reports of BP persistence were compared for methodological approaches, including data source, duration of follow-up, allowed gap for persistence, and presentation of results. Medication persistence. Comparisons among reports of BP persistence for weekly and monthly formulations revealed inconsistent definitions and a variety of methods. Persistence analyses varied greatly, particularly in allowed gaps and adjustment for demographic and clinical characteristics that affected results. Persistence with weekly dosing was 179-249 days, with 24-78% remaining on treatment at 1 year. Analyses of persistence with monthly treatment was complicated by the variety of gap lengths (30-90 days). The studies reviewed had many limitations, including lack of an established threshold for efficacy, inadequacy of information in databases, and potential biases in case selection (treatment-naive or experienced). The limitations of published studies reveal the need for a more consistent approach to medication persistence analyses using claims databases to allow for comparison across reports. The analysis plan should present definitions of all terms, details of all methods and types of adjustments needed for demographic and clinical characteristics, as well as specify allowed gaps between refills. These approaches would improve clinical utility of data describing BP persistence and its impact on fracture risk.

Fourteen reports utilizing data from de-identified administrative databases were reviewed. Studies contained at least one measure of patient persistence or compliance with bisphosphonates or bisphosphonates and other anti-osteoporosis medications. These studies confirm that women with osteoporosis have suboptimal persistence and compliance rates with bisphosphonate therapy.